Chemosensitivity and its association with exercise ventilation inefficiency in patients with chronic coronary syndromes compared to heart failure

Background Inefficient ventilation, namely a high ventilation/carbon dioxide production (VE/VCO2) slope or exertional oscillatory ventilation (EOV) are a well established predictor for disease progression and mortality in patients with chronic heart failure (HF). Increased chemosensitivity has been suggested to contribute to their exaggerated ventilatory drive. The association of markers of peripheral and central chemosensitivity with inefficient ventilation in patients with chronic coronary syndromes (CCS) compared to patients with HF has not been studied. Method Four study groups were recruited: Patients with HF, patients with CCS, old healthy controls (age>45 years) and young healthy controls (age>20 years and <35 years). A cardiopulmonary exercise test (CPET) on a cycle ergometer was performed to exhaustion with breath-by-breath analysis of end-tidal partial pressure of carbon dioxide (PETCO2). From this, the ventilation to carbon dioxide production (VE/VCO2) slope was determined. EOV was diagnosed based on established criteria. For the two patient groups, a VE/VCO2 slope ≥36 in a recent CPET (<4 weeks) was an inclusion criteria. The rebreathing method by Duffin (1) was used to determine the ventilatory threshold (VRT) and slope during a hyperoxic (150 mmHg O2) and during a hypoxic (50 mmHg O2) rebreathing test in sitting resting position to exhaustion or discomfort to determine central and peripheral chemosensitivity. Results Each group included 15 participants. In patients with HF and CCS, median left ventricular ejection fraction was 40% and 60%, and left ventricular end-diastolic volume index was 75.5 and 46.2 ml/m2, respectively. Median VE/VCO2 slopes were 39.6 and 39.0 and EOV was present in 33% and 7% in patients with HF and CCS, respectively. VE/VCO2 slopes in patients were significantly higher (as per inclusion criteria) than in old and young controls with 30.5 and 28.0, respectively (Figure 1). Both patient groups had similarly reduced hyperoxic VRT (at PETCO2 42.0 and 43.2 mmHg) compared to 46.0 and 48.8 mmHg in the old and young controls (p=0.002 for HF vs. old controls and p=0.01 for CCS vs. old controls, Figure 1). Hypoxic VRT was with 41.6 and 39.6 mmHg in patients with HF and CCS insignificantly lower compared to old controls with 42.5 mmHg. There were significant linear associations between hypoxic and hyperoxic VRT within all groups (p<0.05, Figure 2), however, not between VE/VCO2 slope and neither peripheral nor central VRT (Figure 2). Conclusion Central chemosensitivity is similarly heightened in patients with CCS and abnormal VE/VCO2 slopes, compared to patients with HF, suggesting a similar contribution to exercise ventilation inefficiency despite the absence of HF signs and symptoms. The higher prevalence of EOV in patients with HF confirms other studies and may indicate their lower cardiac output and higher circulatory delay compared to patients with CCS.